Currently, microbiological proteases, along with lipases, are the most significant enzymes for biotechnology. They are produced in great quantity and since they are qualitatively diversified, they can be successfully applied in various branches of industry, including medicine. For several decades, the number as well as the significance of studies on extremophilic proteases have been growing. Extremophilic proteases are isolated from extremophiles which, given their unique kinetic and structural adaptations, can be used at low and high temperatures and in extreme environments (alkaline, acidic, saline). These enzymes have already enriched the range of commercial proteases and the studies on their properties in relation to their structural features stimulated a rational engineering of conventional proteases, aimed at enhancing their ability to adapt to specific conditions. In the chapter below, we characterized selected representatives of this most significant, in terms of economy, group of extremophilic proteases and discussed possible directions for their application in biotechnology.